Heart rhythm disorders (arrhythmias) result in significant morbidity and mortality. The need for improving the management of several types of complex arrhythmias has demanded a better understanding of these disorders particularly in relation to underlying anatomy and physiological outcome. This requisite has led to employing multiple noninvasive as well as catheter-based imaging techniques before, during, or after catheterization procedures that are however performed independent of one another. As a result of NIH funding for four years, we successfully developed a prototype catheter system and relevant methods for novel fusion of electrical activity with true cardiac anatomy acquired during catheterization. The objective of this competing continuation application is to develop a catheter-based, cardiac electrophysiological imaging system that not only maps single-beat electrical activity at multiple endocardial sites, but also detects several physiologic parameters and brings them all into the same anatomical reference. The hypothesis is that a noncontact catheter system, that carries both (1) a multielectrode probe for detecting intracavitary potentials from multiple directions and (2) a central echocardiographic transducer for acquiring three-dimensional cardiac anatomy, can provide intracardiac multimodal imaging capabilities that grant coordinated measures of electrical activity, anatomy, function, myocardial blood flow, and hemodynamics. Therefore, we will: (1) further develop a noncontact catheter-system and expand its hardware capabilities for multimodal intracardiac imaging; (2) advance novel mathematical methods to derive several cardiac physiologic parameters from images recorded by the integrated catheter system; and (3) validate the multimodal catheter imaging system and associated methods in canine heart models relevant to clinical situations. The catheter system can be introduced into the heart without surgery, and can provide safe and efficient means to diagnose causes and consequences of abnormal heart rhythms and to elucidate effects of therapy. The proposed research focuses on image-guided diagnosis with the belief that diagnostic physiologic parameters would further complement electric-anatomic end-points during cardiac catheterization. In line with a Bioengineering Research Grant, the research develops a system the outcome of which is to improve the benefit-risk and benefit-cost relationships of patient care and advance heart rhythm-related research.